Chromosomal localization of the proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex.

Proteasomes are the multi-subunit protease thought to play a key role in the generation of peptides presented by major histocompatibility complex (MHC) class I molecules. When cells are stimulated with interferon gamma, two MHC-encoded subunits, low molecular mass polypeptide (LMP) 2 and LMP7, and the MECL1 subunit encoded outside the MHC are incorporated into the proteasomal complex, presumably by displacing the housekeeping subunits designated Y, X, and Z, respectively. These changes in the subunit composition appear to facilitate class I-mediated antigen presentation, presumably by altering the cleavage specificities of the proteasome. Here we show that the mouse gene encoding the Z subunit (Psmb7) maps to the paracentromeric region of chromosome 2. Inspection of the mouse loci adjacent to the Psmb7 locus provides evidence that the paracentromeric region of chromosome 2 and the MHC region on chromosome 17 most likely arose as a result of a duplication that took place at an early stage of vertebrate evolution. The traces of this duplication are also evident in the homologous human chromosome regions (6p21.3 and 9q33-q34). These observations have implications in understanding the genomic organization of the present-day MHC and offer insights into the origin of the MHC.

蛋白酶体（proteasome）是一类多亚基蛋白酶，被认为在主要组织相容性复合体（major histocompatibility complex, MHC）I类分子呈递的肽段生成过程中发挥关键作用。当细胞经γ干扰素（interferon gamma）刺激后，两个由MHC编码的亚基——低分子量多肽（low molecular mass polypeptide, LMP）2和LMP7，以及MHC区域外编码的MECL1亚基，会被整合进入蛋白酶体复合物，其机制推测为分别替换被命名为Y、X、Z的管家亚基。上述亚基组成的改变似乎能促进I类分子介导的抗原呈递，推测其机制为改变了蛋白酶体的切割特异性。本研究显示，编码Z亚基的小鼠基因（Psmb7）定位在2号染色体的着丝粒旁区域（paracentromeric region）。对Psmb7基因座邻近的小鼠基因座进行分析后发现，2号染色体的着丝粒旁区域与17号染色体上的MHC区域，极有可能起源于脊椎动物进化早期发生的一次基因复制事件。该复制事件的痕迹在同源的人类染色体区域（6p21.3和9q33-q34）中也同样可见。上述发现有助于理解现代MHC的基因组组织结构，并为阐明MHC的起源提供了新的研究视角。